Platelet inhibition and secondary prevention in cardiac surgery patients

Sammanfattning: ABSTRACT Background and objective Coronary artery bypass grafting (CABG) is the most common cardiac surgery procedure. Dual antiplatelet therapy (DAPT) reduces the risk for ischaemic events in patients with acute coronary syndrome (ACS) but increases the bleeding risk, both for spontaneous bleedings and procedure-related bleedings for the subset of ACS patients undergoing urgent CABG. Statins, beta-blockers, and renin-angiotensin-system (RAS) inhibitors are commonly prescribed after CABG but the scientific evidence for their use after CABG is scarce. The objective of this thesis is to investigate how different aspects of pharmacotherapy are associated with short- and long-term risk for adverse events after CABG. Methods Study I: Platelet function before and after cardiac surgery was analysed using impedance aggregometry in patients treated with acetylsalicylic acid and the P2Y12-inhibitor ticagrelor. Associations between pre- and postoperative platelet function and risk for severe postoperative bleeding were investigated. Study II-IV: Individual patient data from the Swedish Cardiac Surgery Registry, the National Patient Register, the Swedish Prescribed Drug Register, LISA register and the Cause of Death Register was merged to obtain data on procedural aspects, baseline comorbidities, adverse events and mortality after CABG. Study II investigated associations between use of statins, beta-blockers, RAS-inhibitors and platelet inhibitors and mortality risk. Study III investigated if the combination of ASA and ticagrelor was associated with improved clinical outcome compared to ASA monotherapy in patients with acute coronary syndrome undergoing CABG. Study IV investigated the associations between post-discharge major bleeding and myocardial infarction respectively with subsequent mortality risk. Results Study I: Postoperative platelet aggregation induced by adenosin diphosphate (ADP) had an area under curve (AUC) of 0.75 (95% CI 0.62-0.87) in predicting severe bleeding. The corresponding value for preoperative testing was AUC of 0.77 (95% CI 0.65-0.89). Study II: Utilization of secondary prevention medication was high early after CABG but decreased significantly over time. Ongoing use of statins, RAS inhibitors and platelet inhibitors were associated with reduced mortality risk after CABG. Use of beta-blockers was not associated with lower mortality risk. Study III: The combination of acetylsalicylic acid (ASA) and ticagrelor was not associated with lower risk for ischaemic events but increased the bleeding risk compared with ASA monotherapy. Study IV: Post-discharge major bleeding was associated with increased mortality risk, comparable to the increase in mortality risk associated with post-discharge myocardial infarction. Conclusions Adding a postoperative test of platelet aggregation did not improve accuracy in predicting severe bleeding. Improving long-term utilization of statins, RAS inhibitors and platelet inhibitors poses an opportunity to improve long-term survival after CABG. Prospective, randomized controlled trials are warranted to establish the clinical outcome of DAPT with ticagrelor after CABG in ACS patients, especially considering the increased mortality risk associated with post-discharge major bleeding events.